Abstract
Early in the HIV epidemic, lipodystrophy, characterized by subcutaneous fat loss (lipoatrophy), with or without central fat accumulation (lipohypertrophy), was recognized as a frequent condition among people living with HIV (PLWH) receiving combination antiretroviral therapy. The subsequent identification of thymidine analogue nucleoside reverse transcriptase inhibitors as the cause of lipoatrophy led to the development of newer antiretroviral agents; however, studies have demonstrated continued abnormalities in fat and/or lipid storage in PLWH treated with newer drugs (including integrase inhibitor-based regimens), with fat gain due to restoration to health in antiretroviral therapy-naive PLWH, which is compounded by the rising rates of obesity. The mechanisms of fat alterations in PLWH are complex, multifactorial and not fully understood, although they are known to result in part from the direct effects of HIV proteins and antiretroviral agents on adipocyte health, genetic factors, increased microbial translocation, changes in the adaptive immune milieu after infection, increased tissue inflammation and accelerated fibrosis. Management includes classical lifestyle alterations with a role for pharmacological therapies and surgery in some patients. Continued fat alterations in PLWH will have an important effect on lifespan, healthspan and quality of life as patients age worldwide, highlighting the need to investigate the critical uncertainties regarding pathophysiology, risk factors and management.
Highlights
Abstract | Early in the HIV epidemic, lipodystrophy, characterized by subcutaneous fat loss, with or without central fat accumulation, was recognized as a frequent condition among people living with HIV (PLWH) receiving combination antiretroviral therapy
Fat alteration became a major concern in Western countries in the mid-1990s, when people living with HIV (PLWH) receiving combination antiretroviral therapy
(cART) developed a condition of severe subcutaneous lipoatrophy, which was termed lipodystrophy[4]. Some of these PLWH with lipodystrophy had fat gain in the trunk and neck. These conditions were common in PLWH who were treated with older-generation thymidine analogue nucleoside reverse transcriptase inhibitors (NRTIs; such as zidovudine and stavudine)[5] (Box 1) and early protease inhibitors (PIs; such as indinavir and full-dose ritonavir)
Summary
FRM EQU201903007868, ICAN, RHU CARMMA, Paris, France. 3Department of Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA. 4Department of Infectious Diseases, HIV Infection Unit, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. 5HIV/AIDS Unit and LIPO & Metabolism Group, Infectious Disease Division, Geneva. The imaging sub-study of the ACTG study A5257 demonstrated a mean CT-quantified VAT gain of 26% 96 weeks after treatment initiation, with a 13% limb fat gain and 20% SAT gain, which did not vary significantly between individuals randomized to receive raltegravir, ritonavir-boosted darunavir or ritonavir-boosted atazanavir[56] These findings suggest a disproportionate gain in VAT compared with SAT among persons receiving PIs or an INSTI in combination with newer-generation NRTIs. in a subsequent analysis, women had a greater increase in waist circumference on raltegravir versus PIs than men[57], suggesting sex differences in drug effects. In studies from the Modena HIV Metabolic Clinic, DXA-quantified trunk fat continuously and steadily increased, whilst lean mass consistently decreased, in PLWH using long-term cART, which was observed in both men and women and across all age groups[59]. As VAT gains of as little as 5% have been associated with an increased risk of metabolic syndrome[60] and trunk fat accumulation has been associated with short-term mortality risk in PLWH61, patients with increased trunk adiposity have an increased risk of cardiometabolic diseases and could benefit from the screening and treatment of cardiovascular and metabolic risk factors
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